Oral premalignant lesions (OPLs) offer a unique human model for the study of biobehavioral risk factors because these lesions are associated with a well-defined risk for subsequent cancer development and are easy to monitor. Epidemiologic data suggest that tobacco and alcohol use, as well as human papillomavirus (HPV) infection of the upper aerodigestive tract, can contribute to the development of oral lesions. However, because not all lesions progress to cancer, the presence of co-factors (such as immune dysregulation) are likely to be involved in disease progression. Accumulating data indicate that psychosocial (e.g., stress) and behavioral (e.g., smoking) factors are associated with immune alterations, which could have implications for oral disease progression. Genetic factors also influence immune response and may partially explain differences in disease risk. Guided by a biobehavioral model of cancer risk, the proposed project employs a prospective, longitudinal design to evaluate the potential interrelations among psychosocial and behavioral risk factors, host immune factors, and progression of OPLs. Participants will be recruited from a large, urban dental clinic, and will complete psychological, behavioral, and immunologic assessments at diagnosis and at 6- and 12-months post-diagnosis. The specific aims of the study are to: 1) examine psychosocial (e.g., stress) and behavioral (e.g., smoking) correlates of immune status in patients with OPLs; 2) investigate the relationship between host immune factors and disease status; and 3) explore whether HLA genotypes are associated with disease risk. Building upon the candidate's training in health psychology, immunology, and cancer prevention and control, the proposed application will examine physiological consequences of the stress and coping response among individuals with OPLs, with a view to elucidating the biobehavioral pathways that may contribute to disease risk and progression. Data collected will help shape the development of psychosocial and behavioral interventions designed to reduce cancer risk and morbidity. The initial year of the award will be directed toward launching the proposed research project and obtaining pilot data in support of an R01 application to be submitted during the second year. Receipt of this award will help the candidate to establish an independent research program by providing protected time and necessary resources as the candidate transitions from a mentored position.